Skip to main content

Singapore Flap (Pudendal Thigh Fasciocutaneous Flap)

The Singapore flap — also called the pudendal thigh fasciocutaneous flap (PTF) — is a sensate, axial-pattern fasciocutaneous flap based on the terminal branches of the superficial perineal artery (the continuation of the internal pudendal artery), harvested from the groin crease just lateral to the labia majora. First described by Wee and Joseph at Singapore General Hospital in 1989 for vaginal reconstruction, it has become a workhorse for bilateral neovaginal construction, complex perineal fistula repair, vulvar oncologic reconstruction, obstetric-fistula vaginal-stenosis management, and perineal burn-contracture release, with 100% complete flap survival in the largest dedicated series (31 flaps).[1][2]

Singapore vs lotus petal — keep them distinct

The "Singapore flap" name is sometimes also applied to the gluteal-fold lotus petal flap (Yii and Niranjan 1996). WARWIKI keeps these as separate pages because the donor sites and primary indications differ: the Wee–Joseph groin-crease / upper medial thigh flap on this page is the workhorse for bilateral neovagina and posterior vaginal reconstruction, while the gluteal-fold IPA-perforator lotus petal flap is the workhorse for vulvar oncologic reconstruction, ELAPE pelvic-floor coverage, and male perineal / scrotal reconstruction.

Nomenclature​

The same flap appears in the literature under several names reflecting anatomical basis and design variations:

NameOrigin / framing
Singapore flapOriginal eponymous designation (Wee & Joseph, Singapore General Hospital, 1989)[2]
Pudendal thigh fasciocutaneous (PTF) flapDescriptive anatomical name
Internal pudendal artery perforator (IPAP) flapModern perforator-based nomenclature (Yii & Niranjan 1996) — refines the design around explicitly identified perforators[3]
Lotus petal flapWhen the cumulative perineal flap designs from gluteal fold to genitocrural sulcus resemble lotus petals — see the dedicated lotus petal page for the gluteal-fold variant[4]
Gluteal-fold flapWhen the lower (gluteal-fold) "petal" is used — donor scar hidden in the gluteal fold

These terms are sometimes used interchangeably. WARWIKI uses Singapore flap / PTF for the groin-crease / upper-medial-thigh design described on this page.

Vascular Anatomy​

The Singapore flap is a three-vascular-territory fasciocutaneous flap with its pedicle situated close to the midline. The definitive cadaveric description was provided by Tham and colleagues (2010) using lead-oxide injection in 5 cadavers.[5]

Sequential blood supply to the pelvic-floor integument (medial → lateral):

  1. Posterior labial / posterior scrotal arteries — terminal branches of the internal pudendal artery; located deep to Colles' fascia; the primary pedicle of the Singapore flap.
  2. Cutaneous branches of the anterior branch of the obturator artery — superficial to Colles' fascia; supply the middle territory.
  3. Branches of the external pudendal arteries — superficial to Colles' fascia; supply the lateral / distal territory.

All three vascular territories run close to the midline, medial to the originally described PTF design. Two clinical implications follow directly:

  • The flap should be designed more medially than originally described to optimize vascular capture.
  • The distal (lateral) third of the flap is fed by the most precarious territory (external pudendal branches), explaining the well-documented problem of apical necrosis in larger flaps.[5][6]

Perforator anatomy. Color-Doppler ultrasound in 15 subjects (Giroux 2021) identified 3–5 perforators in the perineal anogenital triangle, with the internal-pudendal perforator at a mean distance of 27.3 mm from the ischial tuberosity. The ischial tuberosity is the key anatomic landmark for safe medial dissection, and routine preoperative Doppler imaging is not always required in experienced hands — simplifying the procedure for low-resource settings.[3]

A microdissection study (Jin 2009) identified 4 relatively constant perforators in the perineum — inguinal and perineal branches of the superficial external pudendal artery, an anterior-obturator perforator, and a perforator from the lateral branch of the posterior labial artery — forming upper, middle, and lower vascular anastomoses in the deep fascia above the adductor wall.[7]

Sensory innervation. Cutaneous branches of the ilioinguinal, genitofemoral, posterior labial, and posterior femoral cutaneous (rami perineales) nerves lie within the flap territory, making the flap sensate — a defining advantage for functional reconstruction.[7]

Applications in GU and Urogynecologic Reconstruction​

1. Neovagina — congenital vaginal agenesis (MRKH / Müllerian agenesis)​

The original and most extensively described indication. Bilateral PTF flaps are transposed medially and sutured together to create a skin-lined vaginal pouch.

  • Monstrey 2001 — 8 patients with congenital atresia; all 16 flaps survived completely; functional outcome excellent; no stents or dilators required; sensate reconstruction.[1]
  • Selvaggi 2003 — 2 patients with vaginal aplasia and functioning uterus; bilateral PTF + laparotomy for uterovaginal continuity; normal menstruation restored in both; coital satisfaction achieved. Main disadvantage: sebaceous secretion and hair growth (managed with laser depilation).[8]
  • Selçuk 2013 — 6 patients with Müllerian agenesis; PTF flaps thinned with preoperative liposuction; adequate vaginal depth achieved in all.[9]
  • Uccella 2024 — modification using internal-thigh fasciocutaneous flaps (12 × 5 cm) tunneled to a neovagina introitus; sensate, patent neovagina at 2-year follow-up; external genitalia preserved.[10]

Advantages over other neovagina techniques:

FeatureSingapore (PTF)McIndoe (skin graft)Bowel (sigmoid)Vecchietti / dilators
SensateYesNoNoVariable
Stents / dilators requiredNo (or minimal)Yes (prolonged)NoYes (prolonged)
Abdominal surgery requiredNoNoYesYes (laparoscopic)
Natural vaginal angleYesVariableYesVariable
SecretionSebaceousDryMucus (excessive)Dry
Hair growthYes (manageable)NoNoNo
Donor-site morbidityMinimal (groin scar)Thigh / buttock graft siteAbdominalNone
ComplexityLowLowHighLow

2. Neovagina — after oncologic resection (radical vaginectomy / pelvic exenteration)​

Outcomes here are bimodal depending on radiation status:

  • Non-irradiated: Monstrey 2001 reported 5 patients with all 10 bilateral flaps surviving completely with excellent functional outcome.[1]
  • Irradiated: Gleeson 1994 reported disappointing functional results in 8 patients (6 exenteration, 2 radical vaginectomy) — partial apical necrosis in 4, complete bilateral necrosis in 1, and no patient with bilateral flaps or prior pelvic irradiation achieved successful coitus. Long-term sequelae: vulvar pain, chronic discharge, hair growth, and flap protrusion.[6]

This bimodal pattern is the central caveat of the flap: excellent in non-irradiated patients; poor in irradiated pelves, where vascular pedicle and recipient tissues are both compromised. In irradiated fields, raise muscular flaps from outside the radiation territory (gracilis, VRAM) instead.[11][6]

3. Pediatric genital reconstruction​

Joseph 1997 reported the largest pediatric PTF series — 12 patients with bilateral flaps based on the posterior labial artery: 6 with congenital adrenal hyperplasia (CAH), 3 with vaginal atresia, 2 with cloacal deformities, 1 with testicular feminizing syndrome. Technique was simple and reliable with satisfactory functional and cosmetic results, performable as one-stage or staged reconstruction and combinable with correction of associated anomalies.[12]

4. Rectovaginal fistula (RVF) repair​

Used as a unilateral island flap providing both vascularized interposition and epithelial coverage for complex or recurrent RVF:

  • Monstrey 2001 — 4 patients with recurrent / complex RVF, all flaps survived, excellent functional outcome.[1]
  • Lee & Lee 2009 — transverse Singapore flap for a 3 × 3 cm congenital RVF in an 18-month-old infant, simultaneously reconstructing posterior vaginal and anterior rectal walls; functionally and cosmetically satisfactory at 20-month follow-up.[13]

5. Posterior urethral defects in scarred perineum​

Monstrey 2001 used the Singapore flap in 2 patients with posterior urethral defects in heavily scarred perineums where local tissue was insufficient — providing well-vascularized, sensate tissue to a hostile wound bed.[1]

6. Obstetric fistula repair (low-resource settings)​

The Singapore flap has emerged as a particularly valuable adjunct in obstetric fistula surgery in low- and middle-income countries, where vaginal stenosis frequently complicates fistula repair. The flap restores vaginal elasticity required for urethral closure mechanisms.[14][15]

  • Pope 2018 (Malawi) — described the technique for vaginal reconstruction in women with vaginal stenosis and obstetric fistula. The flap is ideal for low-resource settings: reliable, safe, easy to dissect, minimal supply requirements.[14]
  • Browning 2018 — Singapore skin flap used prophylactically with Goh type 4 fistula (n = 45): 46% dry against an expected 19%. In patients with successful closure but persistent severe leakage (n = 24), 71% dry against an expected 26% — supporting the elasticity-restoration mechanism.[15]
  • Pope 2020 — retrospective Malawi review of 69 patients (32 Singapore alone, 20 gracilis alone, 17 both); the authors noted a possible advantage of incorporating the gracilis flap even when the Singapore flap alone was thought sufficient.[16]
  • Maljaars 2022 — follow-up of 60 patients after obstetric fistula repair with vascularized flaps in Malawi: 62% successful closure, 12% full continence; no major complications; quality of life improved despite persistent incontinence.[17]

7. Vulvar oncologic reconstruction​

Appropriate for lateral / hemivulvectomy defects (unilateral) and total vulvectomy defects (bilateral):

  • Höckel & Dornhöfer 2008 recommend pudendal-thigh flaps for medium-size vulvar and partial vaginal defects, with bilateral flaps for complete neovagina.[11]
  • Salgarello 2005 include the pedicled PTF in their algorithm for small-to-medium vulvar defects, alongside V-Y island and gluteal-fold flaps.[18]
  • Han 2023 — 47 patients; 31 received internal pudendal artery perforator (IPAP) flaps (66%) and 16 received PAP / TUG flaps (34%). IPAP flaps had significantly fewer wound complications (12.9% vs 37.5%, p = 0.04).[19]
  • Toulouse Algorithm (Ricotta 2025) proposes perforator flaps (including internal-pudendal-perforator) as first-line for vulvar reconstruction, tailored to defect location and size.[20]

8. Vaginal stenosis (post-radiation)​

Clifton 2017 described the Singapore flap for post-radiation vaginal stenosis after failed conservative management and prior gracilis flap. The flap provides sensate tissue, but ongoing vaginal dilation is imperative — stenosis can recur.[21]

9. Perineal burn-contracture release​

Benito 2012 described the PTF designed as a Y-V advancement for perineal burn contractures, exploiting its thinness, adaptability, and maintained sensitivity.[22]

10. Fournier's gangrene reconstruction​

The Alammar 2026 systematic review (107 studies, 619 patients) identified the pudendal-thigh flap as one of the most commonly utilized flaps for Fournier's gangrene reconstruction, with overall flap loss only 1.6%.[23]

Surgical Technique​

The technique as refined by Monstrey 2001:[1][2]

  1. Patient positioning — lithotomy.
  2. Flap design — skin island marked in the groin crease (labiocrural fold) just lateral to the hair-bearing labia majora, with the base at the perineal body. Typical dimensions 9 × 4 cm to 15 × 6 cm.[6]
  3. Incision and elevation — lateral border incised first; flap elevated from lateral to medial in a subfascial plane including skin, subcutaneous tissue, deep thigh fascia, and the epimysium of the adductor muscles.[6]
  4. Pedicle preservation — dissect medially until the posterior labial artery is identified entering from the medial aspect. The ischial tuberosity is the safe boundary of medial dissection.[3]
  5. Flap islanding — raised as a peninsula flap (skin bridge maintained) or as a true island flap for greater mobility and rotational arc.[1]
  6. Transposition / inset:
    • Bilateral neovagina — both flaps transposed to the midline and sutured together to form a skin-lined cul-de-sac opening at the introitus.[2]
    • Unilateral fistula repair — single flap rotated into the defect for epithelial coverage and / or interposition.[1]
    • Vulvar reconstruction — flap rotated or advanced into the vulvar defect.[11][18]
  7. Donor-site closure — primary, with an inconspicuous scar hidden in the natural groin crease.[1][2]

Technical refinements​

ModificationDescriptionIndication
Liposuction thinning (Selçuk 2013)Two-stage: subcutaneous fat under the planned skin island thinned with liposuction 3 months before flap elevation — produces a thinner flap closer to native vaginal tissue[9]Müllerian agenesis with bulky thighs
Transverse design (Lee & Lee 2009)Transverse orientation to simultaneously reconstruct posterior vaginal and anterior rectal walls[13]Complex congenital RVF
Bilobed design (Ninomiya 2010)Combines gluteal-fold and pudendal-thigh flaps as a bilobed flap — depth + width with hidden donor scars[24]Large vulvar defects requiring vaginal depth
Prefabricated flap (Gürlek 2008)PTF prefabricated with a cervical canal for combined cervical + vaginal reconstruction; preserves uterus for potential pregnancy[25]MURCS syndrome
Y-V advancement (Benito 2012)PTF designed as Y-V advancement[22]Perineal burn-contracture release
IPAP perforator design (Han 2023)Explicit perforator-based design with Doppler mapping; reduced wound-complication rate[19]Vulvar oncologic reconstruction

Outcomes Summary​

IndicationLargest series (n)Flap survivalFunctional outcomeKey complications
Neovagina — congenital agenesis8 (Monstrey 2001)100%Excellent; sensate; no dilatorsHair growth; sebaceous secretion
Neovagina — exenteration, non-irradiated5 (Monstrey 2001)100%ExcellentMinor introital revision
Neovagina — exenteration, irradiated8 (Gleeson 1994)50% partial; 12.5% total necrosisDisappointing — no successful coitusVulvar pain; discharge; protrusion; hair
Complex / recurrent RVF4 (Monstrey 2001)100%ExcellentMinor wound dehiscence
Posterior urethral defect (scarred perineum)2 (Monstrey 2001)100%ExcellentNone reported
Obstetric fistula (low-resource)60 (Maljaars 2022)No major complications62% closure; 12% full continenceMinor wound breakdown (37%)
Pediatric genital anomalies12 (Joseph 1997)100%SatisfactoryNone reported
Vulvar reconstruction (IPAP)31 (Han 2023)100%Acceptable12.9% wound complications
Perineal burn-contracture releaseCase series (Benito)100%SatisfactoryNone reported

Complications and Limitations​

Flap-related

  • Apical (distal) necrosis — the most significant complication, particularly with larger flaps. Anatomically explained by the precarious blood supply of the distal third territory (external-pudendal branches). A delay procedure can mitigate this in large designs.[5][6]
  • Wound dehiscence — minor dehiscence in approximately 5–10%.[1][17]
  • Introital stenosis / narrowing — may require minor revision at the introitus.[1]

Functional

  • Hair growth in flap skin — manageable with preoperative and / or postoperative laser depilation.[1][8][6]
  • Sebaceous secretion — chronic vaginal discharge from sebaceous glands within the flap skin.[8][6]
  • Vulvar protrusion / bulging — bulkier flap base versus labial flaps may cause vulvar bulging after subcutaneous rotation.[11][6]
  • Vulvar pain — reported in some oncologic series.[6]
  • Recurrent vaginal stenosis — particularly in irradiated patients; ongoing dilator regimen necessary.[21]

Critical limitation — irradiated tissue

The Singapore flap performs significantly worse in irradiated patients. Gleeson 1994 reported that no patient with bilateral flaps or prior pelvic irradiation achieved successful coitus, with frequent partial / complete necrosis.[6] Irradiated donor tissue should be strictly avoided; in irradiated pelves, raise muscular flaps from outside the radiation field.[11]

Comparison with Other Vulvovaginal / Perineal Flaps​

FeatureSingapore (PTF)MartiusGracilisVRAMALT
TissueFasciocutaneousFibroadipose (no skin)MyocutaneousMyocutaneousFasciocutaneous
Skin islandYesNoYesYesYes
SensateYesNoNoNoNo
BulkLow–moderateLowModerate–highHighModerate
Stents / dilators requiredNoN/AUsuallyUsuallyUsually
Donor-site morbidityMinimal (groin scar)Very low (labial)Low (thigh)High (abdominal wall; hernia)Moderate (thigh)
Irradiated recipient performancePoorAcceptableAcceptableGoodGood
Best forNeovagina; partial vaginal defects; non-irradiated fistulasFistula interpositionComplex fistulas; large dead spaceExenteration; large defectsLarge defects; irradiated fields
Wound complications (vulvar IPAP head-to-head)12.9%[19]——57.6%[26]—

Technical Pearls​

  • Design more medially than the original description — the three vascular territories all run close to midline.[5]
  • Use the ischial tuberosity as the lateral landmark for safe medial dissection of the internal-pudendal perforator (~27 mm medial).[3]
  • Include the deep fascia and adductor epimysium — suprafascial elevation produces distal necrosis.[6]
  • Doppler the pedicle in radiated or reoperative fields — although routine preoperative imaging is not always required in primary cases.[3]
  • Limit flap length when possible; consider a delay procedure when distal extension is unavoidable.[5]
  • Tubularize with skin inward for neovaginal construction.[2]
  • Avoid in irradiated donor tissue — convert to gracilis or VRAM raised outside the field.[6][11]
  • Plan hair-removal strategy preoperatively (laser depilation) for neovaginal applications.[8]
  • Postoperative dilator regimen is essential for long-term neovaginal patency in oncologic and post-radiation indications.[21]

Key Takeaways​

The Singapore / pudendal thigh fasciocutaneous flap is distinguished from other vulvoperineal flaps by three features: it is sensate, it does not require postoperative dilators for neovaginal construction, and it has minimal donor-site morbidity with scars hidden in natural creases.[1][2] It is the preferred flap for neovaginal construction in non-irradiated patients with congenital vaginal agenesis, achieving 100% flap survival and excellent functional outcome.[1][8] In low-resource settings, it has become an important adjunct to obstetric-fistula repair, restoring vaginal elasticity and improving continence outcomes.[14][15] Its central limitation is poor performance in irradiated fields, where muscular flaps from outside the radiation territory (gracilis, VRAM) are preferred.[11][6] The modern evolution toward an internal pudendal artery perforator (IPAP) design, guided by Doppler ultrasound and the ischial-tuberosity landmark, has further simplified harvest and reduced wound complications.[3][19]

See Also​

References​

1. Monstrey S, Blondeel P, Van Landuyt K, et al. The versatility of the pudendal thigh fasciocutaneous flap used as an island flap. Plast Reconstr Surg. 2001;107(3):719–25. doi:10.1097/00006534-200103000-00011

2. Wee JT, Joseph VT. A new technique of vaginal reconstruction using neurovascular pudendal-thigh flaps: a preliminary report. Plast Reconstr Surg. 1989;83(4):701–9. doi:10.1097/00006534-198904000-00018

3. Giroux PA, Dast S, Assaf N, Lari A, Sinna R. Internal pudendal perforator artery flap harvesting without pre-operative imaging: reliability and approach. J Plast Reconstr Aesthet Surg. 2021;74(6):1355–401. doi:10.1016/j.bjps.2020.12.017

4. Yii NW, Niranjan NS. Lotus petal flaps in vulvo-vaginal reconstruction. Br J Plast Surg. 1996;49(8):547–54. doi:10.1016/s0007-1226(96)90131-7

5. Tham NL, Pan WR, Rozen WM, et al. The pudendal thigh flap for vaginal reconstruction: optimising flap survival. J Plast Reconstr Aesthet Surg. 2010;63(5):826–31. doi:10.1016/j.bjps.2009.02.060

6. Gleeson NC, Baile W, Roberts WS, et al. Pudendal thigh fasciocutaneous flaps for vaginal reconstruction in gynecologic oncology. Gynecol Oncol. 1994;54(3):269–74. doi:10.1006/gyno.1994.1209

7. Jin B, Hasi W, Yang C, Song J. A microdissection study of perforating vessels in the perineum: implication in designing perforator flaps. Ann Plast Surg. 2009;63(6):665–9. doi:10.1097/SAP.0b013e3181999de3

8. Selvaggi G, Monstrey S, Depypere H, et al. Creation of a neovagina with use of a pudendal thigh fasciocutaneous flap and restoration of uterovaginal continuity. Fertil Steril. 2003;80(3):607–11. doi:10.1016/s0015-0282(03)00977-4

9. Selçuk CT, Evsen MS, Ozalp B, Durgun M. Reconstruction of vaginal agenesis with pudendal thigh flaps thinned with liposuction. J Plast Reconstr Aesthet Surg. 2013;66(9):e246–50. doi:10.1016/j.bjps.2013.04.006

10. Uccella S, Galli L, Vigato E, et al. New neovagina-creating technique on the basis of a fasciocutaneous flap for Müllerian agenesis. Fertil Steril. 2024;122(2):382–4. doi:10.1016/j.fertnstert.2024.03.022

11. Höckel M, Dornhöfer N. Vulvovaginal reconstruction for neoplastic disease. Lancet Oncol. 2008;9(6):559–68. doi:10.1016/S1470-2045(08)70147-5

12. Joseph VT. Pudendal-thigh flap vaginoplasty in the reconstruction of genital anomalies. J Pediatr Surg. 1997;32(1):62–5. doi:10.1016/s0022-3468(97)90095-6

13. Lee DT, Lee GK. Transverse Singapore flap for reconstruction of a congenital rectovaginal fistula in an 18-month-old infant. Ann Plast Surg. 2009;63(6):650–3. doi:10.1097/SAP.0b013e31819ae002

14. Pope RJ, Brown RH, Chipungu E, Hollier LH, Wilkinson JP. The use of Singapore flaps for vaginal reconstruction in women with vaginal stenosis with obstetric fistula: a surgical technique. BJOG. 2018;125(6):751–6. doi:10.1111/1471-0528.14952

15. Browning A, Williams G, Petros P. Skin flap vaginal augmentation helps prevent and cure post obstetric fistula repair urine leakage: a critical anatomical analysis. BJOG. 2018;125(6):745–9. doi:10.1111/1471-0528.14953

16. Pope R, Hollier PC, Brown RH, et al. A retrospective review to identify criteria for incorporating the Singapore flap and gracilis muscle flap into obstetric fistula repair. Int J Gynaecol Obstet. 2020;148 Suppl 1:37–41. doi:10.1002/ijgo.13038

17. Maljaars LP, Nundwe W, Roovers JWR, Pope RJ. Follow-up of obstetric fistula repair using Singapore fasciocutaneous flap and/or gracilis muscle flap. Neurourol Urodyn. 2022;41(1):246–54. doi:10.1002/nau.24805

18. Salgarello M, Farallo E, Barone-Adesi L, et al. Flap algorithm in vulvar reconstruction after radical, extensive vulvectomy. Ann Plast Surg. 2005;54(2):184–90. doi:10.1097/01.sap.0000141381.77762.07

19. Han WY, Kim Y, Han HH. A simplified algorithmic approach to vulvar reconstruction according to various types of vulvar defects. Ann Plast Surg. 2023;91(2):270–6. doi:10.1097/SAP.0000000000003597

20. Ricotta G, Russo SA, Ferron G, Meresse T, Martinez A. The Toulouse algorithm: vulvar cancer location-based reconstruction. Int J Gynecol Cancer. 2025;35(4):100065. doi:10.1016/j.ijgc.2024.100065

21. Clifton MM, Gurunluoglu R, Pizarro-Berdichevsky J, Baker T, Vasavada SP. Treatment of vaginal stenosis with fasciocutaneous Singapore flap. Int Urogynecol J. 2017;28(3):493–5. doi:10.1007/s00192-016-3156-8

22. Benito P, De Juan A, Cano M. The pudendal thigh flap as Y-V advanced flap for the release of perineum burns contractures. J Plast Reconstr Aesthet Surg. 2012;65(5):681–3. doi:10.1016/j.bjps.2011.09.039

23. Alammar A, Laing K, Somasundaram J, Wallace DL, Rogers AD. Flap reconstruction following Fournier's gangrene: a systematic review of techniques and outcomes. Burns. 2026;52(3):107888. doi:10.1016/j.burns.2026.107888

24. Ninomiya R, Kishi K, Imanishi N, Nakajima H, Nakajima T. Reconstruction of vulva using pudendal thigh gluteal fold bilobed flap. J Plast Reconstr Aesthet Surg. 2010;63(2):e130–2. doi:10.1016/j.bjps.2009.06.011

25. Gürlek A, Aslan SS, Firat C, Ozturk-Ersoz A, Burak F. Combined cervical and vaginal reconstruction with prefabricated pudendal thigh flap in a case with cervical and vaginal agenesis (MURCS syndrome): a new and original technique. Ann Plast Surg. 2008;61(1):88–93. doi:10.1097/SAP.0b013e31815799d7

26. Eseme EA, Scampa M, Viscardi JA, et al. Surgical outcomes of VRAM vs. gracilis flaps in vulvo-perineal reconstruction following oncologic resection: a proportional meta-analysis. Cancers. 2022;14(17):4300. doi:10.3390/cancers14174300